Vascular Injury

Dr. Charles DeCarli, a neurologist at the University of California, Davis Medical School, is studying the many ways that vascular disease injures the brain. "Twenty years ago, when researchers talked about diseases that affect the blood vessels of the brain, they were referring to strokes." With MRIs and other sensitive brain imaging tools, researchers can now visualize earlier stages of vascular disease in the brain. "We've moved from stroke to so-called silent strokes (strokes without symptoms), to small strokes called lacunae, to a type of very early injury called white matter hyperintensities. This has changed how we think about the ways vascular disease injures the brain."

When large blood vessels in the brain are completely blocked, a stroke occurs, significantly damaging an area of the brain. But earlier, less dramatic blockages can also damage the brain. Dr. DeCarli calls strokes "the tip of the iceberg of cerebrovascular disease." Some smaller vessels of the brain can become blocked, causing damage that produces no immediately discernable symptoms. These silent strokes may occur in as many as one in four people over the age of seventy-five. Other researchers have found that silent strokes double the risk of dementia, and that this kind of cerebrovascular disease intensifies the severity of AD.

Dr. DeCarli is also studying how vascular disease can harm neurons by damaging the axons. As we've seen, neurons communicate with each other by sending signals down the axon of one neuron and across the synapse to be received by the dendrite of a neighboring neuron. In order to better carry an electrical charge, the axon is insulated along its length by myelin, a fatty sheath produced by one of the brain's supporting cell types. By depriving it of blood and nutrients, vascular disease can damage the myelin. When this happens, the electrical impulse cannot travel as efficiently along the axon, and the neuron may not be able to send its signal to the neighboring cell. When neurons stop communicating, cognitive and other problems occur.

Dr. DeCarli and his team have refined MRI techniques to create a visual image of injured myelin around the axons. Damage shows up as bright white areas on a scan—what are called hyperintensities. "We're beginning to see evidence that if the axon is hurt by vascular disease, the whole nerve cell may die."

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Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging